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Review
. 2017 Apr;96(17):e6620.
doi: 10.1097/MD.0000000000006620.

Association of CagA EPIYA-D or EPIYA-C phosphorylation sites with peptic ulcer and gastric cancer risks: A meta-analysis

Qiuping Li  1 , Jingwei Liu, Yuehua Gong, Yuan Yuan
Affiliations
Review

Association of CagA EPIYA-D or EPIYA-C phosphorylation sites with peptic ulcer and gastric cancer risks: A meta-analysis

Qiuping Li et al. Medicine (Baltimore). 2017 Apr.

Abstract

Background: Increasingly, studies have focused on the relationship between Helicobacter pylori (H pylori) cytotoxin associated gene A protein (CagA) Glu-Pro-Ile-Tyr-Ala (EPIYA)-D motifs or multiple EPIYA-C phosphorylation sites and peptic ulcer disease (PUD) or gastric cancer (GC) risk. However, the conclusions have been inconsistent. The aim of this meta-analysis was to evaluate whether 1 CagA EPIYA-D motif or multiple EPIYA-C phosphorylation sites were associated with PUD or GC risk.

Materials and methods: A literature search was performed in PubMed, Web of Science, Wanfang Data, Excerpt Medica Database, and the Chinese National Knowledge Infrastructure database to identify eligible research. We analyzed the odds ratios (OR) and 95% confidence intervals (CI) to assess the strength of association.

Results: Compared with 1 EPIYA-C motif in Asian populations, 1 EPIYA-D site was associated with an increased GC risk (OR=1.91, 95% CI=1.19-3.07, P = .008). However, 1 EPIYA-D motif was not significantly associated with PUD (OR = 0.90, 95% CI = 0.46-1.76, P = .764), gastric ulcer (GU) (OR = 0.85, 95% CI = 0.27-2.63, P = .771), or duodenal ulcer (DU) (OR = 0.89, 95% CI = 0.25-3.16, P = .859) risk. Compared with no more than 1 EPIYA-C motif, multiple motifs were associated with increased PUD (OR = 2.33, 95% CI = 1.29-4.20, P = .005) and DU (OR = 2.32, 95% CI = 1.08-5.00, P = .031) risk in Asia and GC risk in the United States and Europe (OR = 3.28, 95% CI = 2.32-4.64, P < .001). Multiple EPIYA-C sites were not associated with GU risk (OR = 4.54, 95% CI = 0.95-21.83, P = .059). There was no publication bias identified in these comparisons.

Conclusions: In Asia, 1 EPIYA-D motif was significantly associated with increased GC risk. Multiple EPIYA-C motifs were associated with increased PUD and DU risk, particularly in Asia. In the United States and Europe, multiple EPIYA-C motifs were associated with increased GC risk. Therefore, detection of polymorphic CagA EPIYA motifs may improve clinical prediction of disease risk.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

The authors have no conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Flow chart of literature search and study selection. DU = duodenal ulcer, FD = functional dyspepsia, GC = gastric cancer, GU = gastric ulcer, PUD = peptic ulcer disease.
Figure 2
Figure 2
Forest plot of the association between 1 EPIYA-D phosphorylation site and PUD risk. EPIYA = Glu-Pro-Ile-Tyr-Ala, PUD = peptic ulcer disease.
Figure 3
Figure 3
Forest plot of the association between 1 EPIYA-D phosphorylation site and GC risk. EPIYA = Glu-Pro-Ile-Tyr-Ala, GC = gastric cancer.
Figure 4
Figure 4
Forest plot of the association between multiple EPIYA-C phosphorylation sites and PUD risk. EPIYA = Glu-Pro-Ile-Tyr-Ala, PUD = peptic ulcer disease.
Figure 5
Figure 5
Forest plot of the association between multiple EPIYA-C phosphorylation sites and GC risk. EPIYA = Glu-Pro-Ile-Tyr-Ala, GC = gastric cancer.
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